Early diagnosis of lung cancer based on proteome analysis of exhaled breath condensate

A comparative study of the exhaled-breath-condensate (EBC) proteome that was obtained for four donor groups was carried out using ion cyclotron resonance mass spectrometry with electrospray ionization. The groups included subjects with diagnosed lung cancer, chronic obstructive pulmonary disease, community-acquired pneumonia, and healthy nonsmoking control subjects. More than 300 proteins were identified, while 19 of them were found in the EBC samples of the donors who were diagnosed with lung cancer in the early stages and are potentially significant in the development of a diagnostic lung-cancer biomarker panel. It was shown that the EBC protein profiles of different donor groups can be distinguished. It may be possible to highlight a specific protein group that is typical for certain conditions/diseases of the respiratory system. Thus, the EBC analysis could be a promising non-invasive method for early diagnosis of lung cancer.     

Feature selection for OPLS discriminant analysis of cancer tissue lipidomics data

The mass spectrometry‐based molecular profiling can be used for better differentiation between normal and cancer tissues and for the detection of neoplastic transformation, which is of great importance for diagnostics of a pathology, prognosis of its evolution trend, and development of a treatment strategy. The aim of the present study is the evaluation of tissue classification approaches based on various data sets derived from the molecular profile of the organic solvent extracts of a tissue. A set of possibilities are considered for the orthogonal projections to latent structures discriminant analysis: all mass spectrometric peaks over 300 counts threshold, subset of peaks selected by ranking with support vector machine algorithm, peaks selected by random forest algorithm, peaks with the statistically significant difference of the intensity determined by the Mann‐Whitney U test, peaks identified as lipids, and both identified and significantly different peaks. The best predictive potential is obtained for OPLS‐DA model built on nonpolar glycerolipids (Q² = 0.64, area under curve [AUC] = 0.95); the second one is OPLS‐DA model with lipid peaks selected by random forest algorithm (Q² = 0.58, AUC = 0.87). Moreover, models based on particular molecular classes are more preferable from biological point of view, resulting in new explanatory mechanisms of pathophysiology and providing a pathway analysis. Another promising features for OPLS‐DA modeling are phosphatidylethanolamines (Q² = 0.48, AUC = 0.86).     

Spatial characterization of the transversal structure of rotationally symmetric pulsed beams

A simple analytical model is proposed to describe the transversal spatial structure of a tridimensional rotationally symmetric pulsed beam. The spatial behaviour of the pulse amplitude is shown to be linked to its (measurable) second- and higher-order intensity moments, namely, beam width, quality parameter and kurtosis. As an illustrative experimental example, this model has been applied to high-quality TEA CO2 laser pulses. This revised version was published online in November 2006 with corrections to the Cover Date.     

Supermetallization of peptides and proteins during electrospray ionization

The formation of metal‐peptide complexes during electrospray ionization (ESI) is a widely known phenomenon and is often considered to be undesirable. Such effect considerably limits the use of ESI mass spectrometry for the investigation of biologically relevant metal‐peptide compounds that are present in the solution and play critical roles in many bioprocesses such as progression of neurodegenerative diseases. In the article, it is demonstrated that under specific conditions such as high temperature of the desolvating capillary, an interesting effect, which can be called as ‘supermetallization’, occurs. Using a model peptide Αβ amyloid domain 1–16, it was observed that an increase in the temperature of the desolvating capillary results in multiple substitutions of hydrogen atoms by Zn atoms in this peptide. At high temperatures (T ~ 400 °C), up to 11 zinc atoms can be covalently bound to (1–16) Αβ. It was observed that supermetallization of (1–16) Αβ depends on the solvent composition and pH. Supermetallization was also demonstrated for proteins, such as ubiquitin and cytochrome C. That proves that the supermetallization is a general phenomenon for peptides and proteins. For the structural investigation of supermetallized complexes, electron‐capture dissociation (ECD) fragmentation was applied. The effect of hydrogen rearranging during ECD was observed. In addition, quantum chemical calculations were used to estimate the possible structures of different supermetallized complexes. These results allow a more deep understanding of the limitations of the use of ESI mass spectrometry for the investigation of biologically relevant metal‐peptide complexes. Copyright © 2015 John Wiley & Sons, Ltd.     

Mass spectrometric characterization of photooxidative protein modifications in Arabidopsis thaliana thylakoid membranes

Oxidative and nitrosative stress leaves footprints in the plant chloroplast in the form of oxidatively modified proteins. Using a mass spectrometric approach, we identified 126 tyrosine and 12 tryptophan nitration sites in 164 nitrated proteolytic peptides, mainly from photosystem I (PSI), photosystem II (PSII), cytochrome b(6) /f and ATP-synthase complexes and 140 oxidation products of tyrosine, tryptophan, proline, phenylalanine and histidine residues. While a high number of nitration sites were found in proteins from four photosynthetic complexes indicating that the nitration belongs to one of the prominent posttranslational protein modifications in photosynthetic apparatus, amino acid oxidation products were determined mostly in PSII and to a lower extent in PSI. Exposure of plants to light stress resulted in an increased level of tyrosine and tryptophan nitration and tryptophan oxidation in proteins of PSII reaction center and the oxygen-evolving complex, as compared to low light conditions. In contrast, the level of nitration and oxidation of these amino acid residues strongly decreased for all light-harvesting proteins of PSII under the same conditions. Based on these data, we propose that oxidative modifications of proteins by reactive oxygen and nitrogen species might represent an important regulatory mechanism of protein turnover under light stress conditions, especially for PSII and its antenna proteins.     

Differences Between Consecutive Primes

Let p_n be the nth prime. Then this paper is concerned with provingthe following result on the distribution of consecutive primes. The exponent of x in this theorem improves on the work of Heath-Brownwho proved (1) with exponent . Under the Riemann hypothesisone can prove (1) with exponent .The proof of the theorem startswith the Heath-Brown–Linnik identity which leads to aformula giving the number of primes in an interval in termsof coefficients of certain Dirichlet series. I then estimatethe coefficients by using, among other things, the informationwhich can be gained from Montgomery's mean value theorem andHuxley's version of the Hal' asz lemma. Furthermore, by usingfamiliar sieve arguments I am able to discard some of the coefficientsallowing us to gain an improvement over the previous resultof Heath-Brown. 1991 Mathematics Subject Classification: 11N05.     

Interaction between Glutathione and Resveratrol in the Presence of Hydrogen Peroxide: A Kinetic Model

Kinetics and Catalysis - The kinetics of interaction between glutathione (GSH) and unsaturated phenol resveratrol (RVT) in deionized water in the presence of hydrogen peroxide (H2O2) is studied. At...     

Structural Investigation of Biomacromolecules Using Ultrahigh-Resolution Mass Spectrometry and Isotope Exchange

We present a new analysis methodology for arbitrary complex molecular systems using ultrahigh-resolution mass spectrometry and isotope exchange. The kinetics of the hydrogen–deuterium exchange reaction is described for large biomacromolecules. The possible applications of the proposed methodology for the analysis of linear oligosaccharides, proteins, and molecular ensemble of humic acids are discussed.